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Context-dependent role of sirtuin 2 in inflammation

Neural Regeneration research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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The loaded matrix:neurotrophin-enriched hydrogels for stem cell brain repair in Parkinson's disease

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Neural Regeneration research 2025年第8期20卷 2315-2316页

作者： Giulia Comini Eilis Dowd pharmacology&Therapeutics University of GalwayGalwayIreland

More than 200 years after Parkinson's disease was first described by the English surgeon whose name would eventually be given to the condition,available treatments remain purely symptomatic,leaving a critical unmet cl... 详细信息

关键词： clinical loaded eventually

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Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier Department of pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-School for cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma Sciences research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

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Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration research 2025年第1期20卷 195-196页

作者： Hyun Sung Department of neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Medical research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky Center for Brain research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina Schmidt Department of Molecular pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

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ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of cardiovascular Diseases and Medical Innovation Center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

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